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Review

Nature Reviews Neuroscience 8, 766–775 (1 October 2007) | doi:10.1038/nrn2214

Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity

Vittorio Calabrese , Cesare Mancuso , Menotti Calvani , Enrico Rizzarelli , D. Allan Butterfield & Anna Maria Giuffrida Stella

At the end of the 1980s, it was clearly demonstrated that cells produce nitric oxide and that this gaseous molecule is involved in the regulation of the cardiovascular, immune and nervous systems, rather than simply being a toxic pollutant. In the CNS, nitric oxide has an array of functions, such as the regulation of synaptic plasticity, the sleep–wake cycle and hormone secretion. Particularly interesting is the role of nitric oxide as a Janus molecule in the cell death or survival mechanisms in brain cells. In fact, physiological amounts of this gas are neuroprotective, whereas higher concentrations are clearly neurotoxic.